Marketing of Off-Label Drug Use Called into Question

In a soon-to-be-released report, the Government Accountability Office criticizes the Food and Drug Administration’s lax enforcement of laws preventing the marketing of off-label drug use.

Off-label drug use refers to using FDA-approved drugs in ways not yet approved by the agency. This could refer to using a drug to treat a different disease, giving it to a different type of patient, or prescribing a smaller or larger dose.

The practice is legal and common, representing an estimated 20 percent of all prescriptions. Doctors often base their decisions on articles in peer-reviewed journals and textbooks.

Under current FDA regulations, drug companies cannot provide doctors with literature on a drug’s off-label uses. However, they often do so and the FDA does little to monitor the practice. Even when the FDA catches a drug company—which happened just 42 times between 2003 and 2007—it takes an average of seven months to issue a warning.

In February, the FDA issued new guidelines that would allow off-label drug use marketing with several important requirements. The literature must be published in independent, peer-reviewed journals and textbooks, and cannot include content like abstracts, letters to the editor and Phase 1 trials in healthy subjects.

Proponents of the new guidelines say they allow the FDA to better-regulate a practice that has been tacitly accepted for the last decade. They also point to a 1999 court decision that determined that the restriction of off-label marketing was unconstitutional. The decision was vacated a year later on procedural grounds, but the constitutionality of the issue wasn’t addressed.

In February, the FDA released proposed guidelines that would regulate the use of off-label drug marketing. It would require drug companies to provide only independent analysis from respected, peer-reviewed journals and textbooks, and restrict the distribution of promotional materials. Several congressmen were critical of the guidelines, including Calif. Rep. Henry Waxman. “It’s a conflict of interest for the company to be promoting sales when they haven’t been able to establish that a drug is safe and effective through the rigorous FDA process,” he said.

The Government Accountability Office is set to release a report critical of the FDA’s policies on off-label use marketing. The FDA “isn’t keeping track of how drugs are marketed for off-label use, even though marketing for off-label use is illegal and it’s the FDA’s job to enforce that law,” says Iowa Sen. Charles Grassley. “As a result, drug makers aren’t being held accountable for promoting unapproved use of medicine and patient safety is diminished.” Grassley is leading the charge against off-label drug marketing, claiming that raises the costs of Medicare and Medicaid.

In 1999, Federal District Court Royce C. Lamberth ruled in Washington Legal Foundation v. Henney and Shalala that the FDA could not restrict a drug company’s ability to provide information to doctors about a drug’s off-label uses. He determined that provision in the Food and Drug Modernization Act (FDAMA) of 1997 “unconstitutionally restricts protected commercial speech."

In 2000, an appeals court vacated Lamberth’s decision after the FDA announced it had dropped many of its restrictions in the FDAMA. The decision left the constitutionality of whether drug companies could provide information on off-label uses unclear.

Randall S. Stafford, associate professor of medicine at the Stanford Prevention Research Center, calls for greater FDA regulation of off-label drug use. He explains the dangers of the practice: “It undercuts expectations that drug safety and efficacy have been fully evaluated. When newer, more expensive drugs are used off-label, it increases health care costs. It undermines the incentives for manufacturers to perform rigorous studies—and instead subtly encourages them to game the system by seeking approval for secondary indications for which clinical trials are less complicated and less expensive. And off-label use may discourage evidence-based practice.”

Professors Doriane Coleman and Philip Rosoff of Duke’s Trent Center for Bioethics, Humanities and History of Medicine believe that allowing drug companies to distribute literature will lead to poorly-informed choices by doctors. “For off-label uses to be appropriate, however, doctors must get their information from disinterested sources,” they write. “The proposed rule revision is dangerous precisely because it reverses the FDA’s historical course and holds out self-interested drug companies as reliable sources of information about off-label uses of their drugs.”

Marc Shapiro, a lawyer dedicated to food and drug law, wrote a letter in response to the Coleman and Rosoff piece. He writes that the new guidelines set forth by the FDA, which have been the de facto regulations since Judge Lamberth’s 1999 decision, are wise and should be officially put into law.